# Exploring tear fluid biomarkers and the ocular surface in thyroid eye disease

## TL;DR

This study found that tear fluid biomarkers CCL2 and CD40L are elevated in thyroid eye disease patients, suggesting their potential for diagnosis and linking to ocular discomfort.

## Contribution

The study identifies CD40L and CCL2 as novel tear fluid biomarkers for diagnosing thyroid eye disease and links meibum quality to ocular discomfort.

## Key findings

- Tear fluid levels of CCL2 and CD40L are significantly higher in thyroid eye disease patients compared to those without the disease.
- OSDI scores and tear biomarkers CCL2 and CD40L together can distinguish thyroid eye disease patients with 80% area under the ROC curve.
- Impaired meibum quality is associated with increased ocular discomfort in moderate-to-severe thyroid eye disease.

## Abstract

To examine ocular surface changes and inflammatory tear fluid biomarkers in patients with thyroid eye disease (TED).

We included 106 Graves' disease (GD) patients (36 without TED, 32 with active and 38 with inactive TED) and 106 age‐ and sex‐matched healthy subjects for ophthalmological evaluation, including ocular surface status and Meibomian gland function. Tear fluid was analysed for 40 inflammatory biomarkers by a Luminex multiplex bead assay. The parameters were compared across subgroups.

GD patients with TED had significantly higher median (min–max) Ocular Surface Disease Index (OSDI) score than GD patients without TED, with a median score of 31.4 (0–86.4) compared to 7.3 (0–45.8) (p < 0.01). Eleven of 50 patients with moderate‐to‐severe and sight‐threatening TED had a meibum quality score above seven, compared to none of the 20 patients with mild TED (p = 0.027).

Tear fluid levels of chemokine (C–C motif) ligand 2 (CCL2) were significantly (p = 0.003) higher in GD patients compared to healthy subjects. CD40 ligand (CD40L) and CCL2 were higher in GD patients with TED compared with GD patients without TED (p = 0.002 and 0.013, respectively). As a combined biomarker to distinguish between GD patients with and without TED, OSDI score together with tear fluid levels of CCL2 and CD40L produced an area under the receiver operating characteristic (ROC) curve of 0.80, with sensitivity of 0.69 at a fixed specificity of 0.80.

Our findings demonstrate increased tear fluid levels of CD40L and CCL2 in patients with TED, indicating their potential as diagnostic biomarkers. Increased ocular discomfort in patients with TED could be related to impaired meibum quality.